Receptor-targeted delivery of an intracellular toxin to outer hair cells by fibroblast growth factor.
The presence and distribution of functional, high-affinity receptors for fibroblast growth factors (FGFs) in the neonatal organ of Corti were probed using the intracellular toxin saporin conjugated to basic FGF (FGF-2). FGFs that bind to high-affinity FGF receptors are internalized as part of the normal process of receptor inactivation. The receptor can thus be used for the targeted delivery of molecules conjugated to FGF into the cytoplasm. Incubation of postnatal day 5 (P5) rat organ of Corti cultures with FGF-saporin caused a dose dependent destruction of outer hair cells, Deiters cells and outer pillar cells. Inner hair cells and other cells were unaffected. Organ of Corti cultures at P0 and P10 showed much less damage than at P5. The results suggest that outer hair cells and adjacent supporting cells in the organ of Corti transiently express high-affinity FGF receptors, and that these receptors can mediate the intracellular delivery of bioactive molecules.
Dazert
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S
Department of Surgery/Otolaryngology, UCSD School of Medicine and Veterans Administration Medical Center, La Jolla, CA 92093-0666, USA.
Baird
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A
Ryan
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AF
D000818:Animals; D000831:Animals, Newborn; D003593:Cytoplasm / Q000187:drug effects / Q000378:metabolism; D004337:Drug Carriers; D016222:Fibroblast Growth Factor 2 / Q000737:chemistry / Q000633:toxicity*; D018072:Hair Cells, Auditory, Outer / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D000922:Immunotoxins / Q000633:toxicity*; D009699:N-Glycosyl Hydrolases; D009924:Organ Culture Techniques; D009925:Organ of Corti / Q000254:growth & development / Q000378:metabolism*; D010940:Plant Proteins / Q000737:chemistry / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020794:Receptor Protein-Tyrosine Kinases / Q000187:drug effects*; D051497:Receptor, Fibroblast Growth Factor, Type 2; D017468:Receptors, Fibroblast Growth Factor / Q000187:drug effects*; D054789:Ribosome Inactivating Proteins, Type 1; D000076985:Saporins; D003689:Vestibular Nucleus, Lateral / Q000187:drug effects / Q000473:pathology
D004337:Drug Carriers; D000922:Immunotoxins; D010940:Plant Proteins; D017468:Receptors, Fibroblast Growth Factor; D054789:Ribosome Inactivating Proteins, Type 1; D016222:Fibroblast Growth Factor 2; C496356:Fgfr2 protein, rat; D020794:Receptor Protein-Tyrosine Kinases; D051497:Receptor, Fibroblast Growth Factor, Type 2; D009699:N-Glycosyl Hydrolases; D000076985:Saporins